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Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification.
J Biol Chem 2012; 287(21):17860-9JB

Abstract

With regard to Hedgehog signaling in mammalian development, the majority of research has focused on Gli2 and Gli3 rather than Gli1. This is because Gli1(-/-) mice do not show any gross abnormalities in adulthood, and no detailed analyses of fetal Gli1(-/-) mice are available. In this study, we investigated the physiological role of Gli1 in osteogenesis. Histological analyses revealed that bone formation was impaired in Gli1(-/-) fetuses compared with WT fetuses. Gli1(-/-) perichondrial cells expressed neither runt-related transcription factor 2 (Runx2) nor osterix, master regulators of osteogenesis, in contrast to WT cells. In vitro analyses showed that overexpression of Gli1 up-regulated early osteogenesis-related genes in both WT and Runx2(-/-) perichondrial cells, and Gli1 activated transcription of those genes via its association with their 5'-regulatory regions, underlying the function of Gli1 in the perichondrium. Moreover, Gli1(-/-);Gli2(-/-) mice showed more severe phenotypes of impaired bone formation than either Gli1(-/-) or Gli2(-/-) mice, and osteoblast differentiation was impaired in Gli1(-/-);Gli3(-/-) perichondrial cells compared with Gli3(-/-) cells in vitro. These data suggest that Gli1 itself can induce early osteoblast differentiation, at least to some extent, in a Runx2-independent manner. It also plays a redundant role with Gli2 and is involved in the repressor function of Gli3 in osteogenesis. On the basis of these findings, we propose that upon Hedgehog input, Gli1 functions collectively with Gli2 and Gli3 in osteogenesis.

Authors+Show Affiliations

Center for Disease Biology and Integrative Medicine, University of Tokyo, Tokyo 113-0033, Japan. hojo@bmw.t.u-tokyo.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22493482

Citation

Hojo, Hironori, et al. "Gli1 Protein Participates in Hedgehog-mediated Specification of Osteoblast Lineage During Endochondral Ossification." The Journal of Biological Chemistry, vol. 287, no. 21, 2012, pp. 17860-9.
Hojo H, Ohba S, Yano F, et al. Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification. J Biol Chem. 2012;287(21):17860-9.
Hojo, H., Ohba, S., Yano, F., Saito, T., Ikeda, T., Nakajima, K., ... Chung, U. I. (2012). Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification. The Journal of Biological Chemistry, 287(21), pp. 17860-9. doi:10.1074/jbc.M112.347716.
Hojo H, et al. Gli1 Protein Participates in Hedgehog-mediated Specification of Osteoblast Lineage During Endochondral Ossification. J Biol Chem. 2012 May 18;287(21):17860-9. PubMed PMID: 22493482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification. AU - Hojo,Hironori, AU - Ohba,Shinsuke, AU - Yano,Fumiko, AU - Saito,Taku, AU - Ikeda,Toshiyuki, AU - Nakajima,Keiji, AU - Komiyama,Yuske, AU - Nakagata,Naomi, AU - Suzuki,Kentaro, AU - Takato,Tsuyoshi, AU - Kawaguchi,Hiroshi, AU - Chung,Ung-il, Y1 - 2012/04/09/ PY - 2012/4/12/entrez PY - 2012/4/12/pubmed PY - 2012/7/24/medline SP - 17860 EP - 9 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 287 IS - 21 N2 - With regard to Hedgehog signaling in mammalian development, the majority of research has focused on Gli2 and Gli3 rather than Gli1. This is because Gli1(-/-) mice do not show any gross abnormalities in adulthood, and no detailed analyses of fetal Gli1(-/-) mice are available. In this study, we investigated the physiological role of Gli1 in osteogenesis. Histological analyses revealed that bone formation was impaired in Gli1(-/-) fetuses compared with WT fetuses. Gli1(-/-) perichondrial cells expressed neither runt-related transcription factor 2 (Runx2) nor osterix, master regulators of osteogenesis, in contrast to WT cells. In vitro analyses showed that overexpression of Gli1 up-regulated early osteogenesis-related genes in both WT and Runx2(-/-) perichondrial cells, and Gli1 activated transcription of those genes via its association with their 5'-regulatory regions, underlying the function of Gli1 in the perichondrium. Moreover, Gli1(-/-);Gli2(-/-) mice showed more severe phenotypes of impaired bone formation than either Gli1(-/-) or Gli2(-/-) mice, and osteoblast differentiation was impaired in Gli1(-/-);Gli3(-/-) perichondrial cells compared with Gli3(-/-) cells in vitro. These data suggest that Gli1 itself can induce early osteoblast differentiation, at least to some extent, in a Runx2-independent manner. It also plays a redundant role with Gli2 and is involved in the repressor function of Gli3 in osteogenesis. On the basis of these findings, we propose that upon Hedgehog input, Gli1 functions collectively with Gli2 and Gli3 in osteogenesis. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/22493482/Gli1_protein_participates_in_Hedgehog_mediated_specification_of_osteoblast_lineage_during_endochondral_ossification_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=22493482 DB - PRIME DP - Unbound Medicine ER -